Effervescent dosage forms are one possible vehicle for the administration of drugs. Effervescence may be used to provide some degree of taste-masking. Prior to administration to a patient, an effervescent composition is dissolved and/or dispersed in e.g. an aqueous medium, such as drinking water. Dissolution and/or dispersion takes place directly or rapidly, with effervescence to give an agreeable presentation of the drug in the form of a solution which is suitable to drink. Effervescent dosage forms are particularly suitable for patients finding difficulty in swallowing tablets or disliking tablets.
The dissolution upon effervescence of a multiple unit tablet that gives a dispersion of drug particles, or of individual units comprising the drug may cause problem due to the density of the units and/or the density of coating layers surrounding the units. One problem might be that a majority of the individual units are sinking to the bottom of the drinking glass during or/and after effervescence, but prior to administration. These sinking units make it difficult for the patient to drink the dispersion and to receive the complete dose because a great number of the drug containing units will remain in the glass.
A further problem with effervescent tablets is the composition of effervescent tablet excipients which might cause problem to the incorporated drug. For instance, the use of an acidic substance in the effervescent composition presents a problem, if the drug is an acid susceptible compound, such as a proton pump inhibitor. The prior art has already taught that such an acid susceptible drug is best protected by an enteric coating layer. There are different enteric coating layered preparations of for instance omeprazole as well as of other proton pump inhibitors described in the prior art, e.g. U.S. Pat. No. 4,786,505 (AB Hassle). A tableted multiple unit dosage form must also fulfill standard requirement on enteric coated articles. A suitable tableted multiple unit dosage form comprising omeprazole is described in EP 95926054.8 (Astra AB). Incorporation of such enteric coated pellets in an effervescent tablet are described in the International patent application WO97/25030 filed on Dec. 20, 1996 (Astra AB).
Other groups of drugs prepared in dosage forms with coating layer(s) are for instance substances irritating the mucosal area, e.g. NSAIDs (Non Steroidal Anti-inflammatory Drugs), and drugs formulated into controlled release dosage forms, e.g. extended release formulations.
Some examples of different effervescent tablets and systems described in the prior art are discussed below.
Effervescent tablets containing acid-sensitive agents have previously been made by coating the acid particles in the acid-base couple with the base to separate the acid-sensitive agent from the acid, see WO 94/21239 (Wehling et al.) Effervescent tablets containing the active substance without any coating layer have also been suggested by Wehling et al.
Another construction principle has been presented, wherein extended release microcapsules are incorporated in an effervescent tablet, see WO 95/27482 (Elan corp.) A further example is the above mentioned WO097/25030.
Stomach-floating hard-gelatine capsules have been described by Simone et al in Pharmacol. Res. 1995, 31(2), 115-19. However, this capsule preparation is not an effervescent dosage form, i.e. the preparation does not comprise any effervescent components.
The expandable controlled release dosage form described in EP 669 129 is using gas development in a dosage form. The tablet swells to such a size that it stays for a prolonged time in the stomach by utilising the gas generated after ingestion of the tablet.
None of the above discussed prior art document describes or discuss problems involved with dense units in an effervescent dosage form, such as an effervescent tablet comprising a plurality of individual units.